Improving vocal communication with a ketogenic diet in a mouse model of autism

Background Deficits in social communication and language development is a hallmark of autism spectrum disorder currently with no cure. Interventional studies using animal models have been very limited in demonstrating improved vocal communication. Autism has been proposed to involve metabolic dysregulation. Ketogenic diet (KD) is a metabolism-based therapy for medically intractable epilepsy, and its applications in other neurological conditions have been increasingly tested. However, how it would affect vocal communication has not been explored. The BTBR mouse strain is considered a model of idiopathic autism. They display robust deficits in vocalization during social interaction, and have metabolic changes implicated in autism. Methods We investigated the effects of KD on ultrasonic vocalizations (USVs) in juvenile and adult BTBR mice during male-female social encounters. Results After a brief treatment with KD, the amount, spectral bandwidth, and much of the temporal structure of USVs were robustly improved in both juvenile and adult BTBR mice. Composition of call categories and transitioning between individual call subtypes was more effectively improved in juvenile BTBR mice. Limitations Although sharing certain attributes, mouse vocalization is unlikely to model all aspects in the development and deficits of human language. KD is highly restrictive and can be difficult to administer, especially for many people with autism who have narrow food selections. Side effects and potential influence on development should also be considered. Future studies are required to tease apart the molecular mechanisms of KD’s effects on vocalization. Conclusions Together, our data provide further support to the hypothesis that metabolism-based dietary intervention could modify disease expression, including core symptoms, in autism.